Anafilaksis (PIT 2008)

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ANAPHYLAXIS:ANAPHYLAXIS:

DIAGNOSIS, TREATMENTDIAGNOSIS, TREATMENT

AND PREVENTIONAND PREVENTION

Heru SundaruHeru Sundaru

Drug Allergy and Anaphylaxis ClinicDivision of Allergy – Clinical immunology

Department of Internal medicine FKUI!SC"

#a$arta



D%FI&I'I(& (F A&A)H*+A,ISD%FI&I'I(& (F A&A)H*+A,IS

Anaphylaxis is a severe- acute- life.threateningAnaphylaxis is a severe- acute- life.threateninggenerali/ed or systemic hypersensitivity reaction0generali/ed or systemic hypersensitivity reaction0

It is commonly- 1ut not al2ays- mediated 1y an allergicIt is commonly- 1ut not al2ays- mediated 1y an allergicmechanism- usually 1y Ig%0mechanism- usually 1y Ig%0

Allergic 3immunologic4 non.Ig%.mediated anaphylaxisAllergic 3immunologic4 non.Ig%.mediated anaphylaxisalso occurs0also occurs0

&on.allergic anaphylactic reactions- formerly called&on.allergic anaphylactic reactions- formerly called

anaphylactoid or pseudo.allergic reactions- may alsoanaphylactoid or pseudo.allergic reactions- may alsooccur0occur0

#ohansson S5( et al #ACI 6778-99:; <:6.=#ohansson S5( et al #ACI 6778-99:; <:6.=



Why we should kow!Why we should kow!

Anaphylaxis can be fatalAnaphylaxis can be fatal

Unpredictable and suddenlyUnpredictable and suddenly

Can happen anywhereCan happen anywhere

Its prevalence increasedIts prevalence increasedMedico legal ?Medico legal ?



&um1er of hospital discharges 2ith the primary diagnosis of

anaphylaxis per 977 777 episodes of hospital discharge and cause

of anaphylaxis



E"#de$#olo%y :E"#de$#olo%y :

)revalence of anaphylaxis

1. 1 : !"" attendees at #$ in U% &'tewart ( #wan)

1**+,

. Anaphylaxis hospital discharge -.+1"".""" &1**1 /

, 1".1"".""" &1**0 -, &'hei2 ( Alves) """,

!. 1!.!" ad3ission for anaphylaxis 1**" """

&4upta) et al. ""!,0. 10 death attributed to anaphylaxis in U% 1** /

""1 &5u3phrey) ""0,



A&"hyl&'#s: "o"ul&(#o s(udy # )A&"hyl&'#s: "o"ul&(#o s(udy # )

ye&*sye&*s Incidence &annual,: 1 per 1"".""" person / year

1!! residents who experienced 1-0 anaphylactic episode :

11+ residents 1 episode 11+ residents 1 episode

1! resident episode 1! resident episode

0 residents ! episode 0 residents ! episode -!6 atopy

+76 allergen identified: food) 3edication and insect sting

-6 allergy consultation 86 hospitali9ation

1 patient died

Yocum, et al. JACI 1999;104:452-6



A&"hyl&'#s #s & se+e*e, l#e-(h*e&(e#%,A&"hyl&'#s #s & se+e*e, l#e-(h*e&(e#%,

%ee*&l#.ed o* sys(e$#/ hy"e*ses#(#+#(y%ee*&l#.ed o* sys(e$#/ hy"e*ses#(#+#(y*e&/(#o*e&/(#o

Anaphylaxis

Allergic anaphylaxis &on.allergic anaphylaxis

Ig%.mediated anaphylaxis &on.Ig%.mediated allergic anaphylaxis

#ohansson S5(- et al0 Allergy 6779>?=;<9:.<68

Wh&( #s &&"hyl&'#s!



Me/h&#s$s ude*ly#% hu$&Me/h&#s$s ude*ly#% hu$&

&&"hyl&'#s&&"hyl&'#s

Human anaphylaxis

ImmunologicIdiopathic

&on.Immunologic

Ig%- Fc@!Ifoods, venoms,

latex, drugs

(ther blood products,

immune aggregates,

drugs

)hysicalexercise, cold

(ther drugs

Simon F%!0 # Allergy Clin Immunol 677=>99;:=.



#licitors of anaphylaxis &including anaphylactoid reactions,#licitors of anaphylaxis &including anaphylactoid reactions,$rugs

oods

$rug and food additives;ccupational substances &e.g. latex,

Ani3al veno3s

Aeroallergens

'e3inal fluidContact urticariogens

5hysical agents &colt) heat) ultraviolet radiation,

#xercise

#chinococcal cyst

'u33ation anaphylaxis

Underlying disease

Co3ple3ent factor 1inactivator deficiency

'yste3ic 3astocytosis

Idiopathic &?,Ring J, Boc!o" # $ Be%en&t. 'i(to) an& cla((i*ication o* ana+%)lai(. In Ana+%)lai(. oati( /oun&ation 2004:12



'he causes of anaphylaxis'he causes of anaphylaxis

Golden DBK, Patterns of anaphylaxis: Acute & late phase features of allergic reactions. In Anaphylaxis.Noartis foundation !""#: $"%



;nset ti3e of reaction in insect veno3 anaphylaxis.;nset ti3e of reaction in insect veno3 anaphylaxis.

&fro3 <oc2ey et al 1*77) with per3ission,&fro3 <oc2ey et al 1*77) with per3ission,

Golden DBK, Patterns of anaphylaxis: Acute & late phase features of allergic reactions. In Anaphylaxis.

Noartis foundation !""#: $"



4rading of anaphylactic reactions according to severity of clinical sy3pto3s4rading of anaphylactic reactions according to severity of clinical sy3pto3s

'y3pto3s

4rade $er3al Abdo3inal =espiratory Cardiovascular

I uitu(

/lu(%ticaiaAngio&ema

II uitu(/lu(%ticaia

Angio&ema notman&ato)3

au(eaCam+ing

R%ino%oea'oa(ene(()(+noea

ac%)ca&ia 120 7+m3Bloo& +e((ue c%ange 20 mm'g ()(tolic3

A%)tmia

III uitu(/lu(%ticaia

Angio&ema notman&ato)3

8omitinge*ecationiaoea

a)ngeal oe&emaBonc%o(+a(mC)ano(i(

%oc!

I8 uitu(/lu(%ticaiaAngio&ema not

man&ato)3

8omitinge*ecationia%oea

Re(+iato) ae(t Ca&iac ae(t

B+m 7eat( +eminuteRing J, Boc!o" # $ Be%en&t. 'i(to) an& cla((i*ication o* ana+%)lai(. In Ana+%)lai(. oati( /oun&ation 2004:12



G*&d#% sys(e$ o* %ee*&l#.edG*&d#% sys(e$ o* %ee*&l#.ed

*e&/(#os 0*o$ 1*ow 23345*e&/(#os 0*o$ 1*ow 23345

4rade $efined byMildMild &s2in and subcutaneous&s2in and subcutaneous

tissue only,>tissue only,>4enerali9ed erythe3a) urticaria)4enerali9ed erythe3a) urticaria)

periorbital oede3a or angiode3a periorbital oede3a or angiode3a

ModerateModerate &features&features

suggesting respiratory)suggesting respiratory)cardiovascular orcardiovascular or

gastrointestinal involve3ent,gastrointestinal involve3ent,

$yspnoea) stridor) whee9e) nausea)$yspnoea) stridor) whee9e) nausea)

vo3iting) di99iness &presyncope,vo3iting) di99iness &presyncope,

'evere'evere &ypoxia) hypotension&ypoxia) hypotension

or neurological co3pro3isedor neurological co3pro3ised

Cyanosis or 'p;Cyanosis or 'p; @ *6) hypotension@ *6) hypotension

&'5 B *" 33 g in adults,)&'5 B *" 33 g in adults,)confusion) collapse) <;C orconfusion) collapse) <;C or

incontinenceincontinence< %e mild ga&e &oe( not e+e(ent ana+%)lai( acco&ing to t%e ational In(titute o* Alleg) an&

In*ection( i(ea(e-*oo& Alleg) an& Ana+%)lai( et"o! IAI-/AA3 &e*inition Bo 23, lo(( o*

con(ciou(ne((; B, ()(tolic 7loo& +e((ue.rown '4A. ACI) ""0:110:!81+rown '4A. ACI) ""0:110:!81+



A&"hyl&'#s /& 6e &(&lA&"hyl&'#s /& 6e &(&l

e able to recogni9e the sy3pto3s

%now and avoid the triggers

ave an e3ergency action plan

Dreat it pro3ptly and appropriately



Suspected cause of death 696 reactionsSuspected cause of death 696 reactions

'ting'ting 08 * wasp) 0 bee) 10 unidentified

EutsEuts ! al3ond) bra9il) 1 ha9el) 1" peanut) + walnut) 11 3ixed orunidentified

oodood 1! 1 banana) chic2pea) fish) - 3il2) crustacean) 1 snail

ood?ood? 17 1 ?fish) - during 3eal) 1 ?grape) ! ?3il2) ! ?nut) 1 ?sherbet)1 ?strawberry) 1 ?yeast) 1 ?nectarine

AntibioticAntibiotic 8 1 ben9ypenicillin) 1" a3inopenicillin) 1 cephalosporin) 1ciprofloxacin) 1 vanco3ycin) a3photericin

AnestheticAnesthetic !- 1* suxa3ethoniu3) 8 vecuroniu3) + attracuriu3) 8 at induction

;ther drug;ther drug 1- ! AC# inhibitor) + E'AI$) - gelatines) prota3ine) vita3in %)

1 $ia3ox &aceta9ola3ide,) 1 etoposide) 1 pethidine) 1 heroin) 12abi2inase) 1 local anaesthetic

ContrastContrast3edia 3edia

11 * iodinated) 1 technetiu3) 1 fluorescein

;ther;ther ! 1 latex) 1 hair dye) 1 hydatid) 1 idiophatic

Pu'phrey ()*, +atal anaphylaxis in the K, $--!!""$. In Anaphylaxis. Noartis +oundation !""#:$$/



"ode of death"ode of death

$rug 'ting ood ood? Male e3ale

<ower airways 11 ! 0 11 1 +

Upper F lower airways + 0 1! ! - 1*

Upper airways 8 7 - ! 1+ 1

'hoc2 F asphyxia 1 0 1 1-

'hoc2 ! 17 ! *

$isse3inatedintravascular coagulation

- 1 1 0

Pu'phrey ()*, +atal anaphylaxis in the K, $--!!""$. In Anaphylaxis. Noartis +oundation !""#:$!"



Interval from exposure to first arrest0 Drug reaction 2ereInterval from exposure to first arrest0 Drug reaction 2ere

fastest- mostly ta$ing less than ? minutesfastest- mostly ta$ing less than ? minutes

Pu'phrey ()*, +atal anaphylaxis in the K, $--!!""$. In Anaphylaxis. Noartis +oundation !""#:$!$



7LINI7AL 8EAT9RES7LINI7AL 8EAT9RES



A&"hyl&'#s sy$"(o$sA&"hyl&'#s sy$"(o$s

M;UD itching swelling of lips andor tongue

D=;AD itching) tightness) closure) hoarseness

'%IE itching) hives) redness) swelling 4UD vo3iting) diarrhea) cra3ps

<UE4 shortness of breath) cough) whee9e

#A=D wea2 pulse) di99iness) passing out

E#U=; headache) visual loss) loss of

consciousness) incontinence) confusion

8*eue/y o o//u**e/e o8*eue/y o o//u**e/e o



8*eue/y o o//u**e/e o8*eue/y o o//u**e/e os#%s ; sy$"(o$s os#%s ; sy$"(o$s o

&&"hyl&'#s<=&&"hyl&'#s<=

Signs B symptomsCutaneous Urticaria B angiodema Flushing )ruritus 2ithout rash!espiratory

Dyspnea- 2hee/e Upper air2ay angioedema !hinitisDi//iness- syncope- hypotensionA1dominal &ausea- vomiting- diarrhea- cramping pain

"iscellaneous Headache Su1sternal pain

Sei/ure

7<?.78?.??6.?

87.=7

8?.?7?7.=79?.67:7.:?

6?.:7

?.<8.=9.6

E (n the 1asis of a compilation of 9<=? patients reported in references 9 through 98

)ercentages are approximations



DIAGNOSISDIAGNOSIS



DIA5&(SIS (F A&A)H*+A,ISDIA5&(SIS (F A&A)H*+A,IS

Clinical diagnosis 1ased on clinical presentation andexposure history

Flushing and tachycardia are invaria1ly present- other

cutaneous symptoms 3hives- itch4 may 1e a1sent

Anaphylaxis may 1e difficult to diagnose- especially 2hen

patients present 2ith 1radycardia 3instead of tachycardia-

2hich is usual4

Gery rarely- patients present only 2ith profound hypotension0

'he exposure to some inciting event is one $ey to the

diagnosis in this rare circumstance

0ie1er'an P0 et al. 2 Allergy 3lin I''unol !""4$$:)#/%!%



DIA5&(SIS (F A&A)H*+A,ISDIA5&(SIS (F A&A)H*+A,IS3contd43contd4

Careful history to identify possi1le causesCareful history to identify possi1le causes

Can 1e confirmed 1y an elevated serum tryptase levelCan 1e confirmed 1y an elevated serum tryptase level

.. specific for mast cell degranulationspecific for mast cell degranulation

.. remains elevated for up to = hoursremains elevated for up to = hours

.. may not 1e elevated- especially inmay not 1e elevated- especially in food allergyfood allergy

!efer to allergist for specific testing!efer to allergist for specific testing

h l # # h# hl l#k l hA h l # # h# hl l#k l h



A&"hyl&'#s #s h#%hly l#kely whe &yA&"hyl&'#s #s h#%hly l#kely whe &y

oe o (he ollow#% > /*#(e*#& &*eoe o (he ollow#% > /*#(e*#& &*e

ul?lledul?lled @@

1. Acute onset of an illness &3inutes to several hours, withinvolve3ent of the s2in) 3ucosal tissue) or both &eg)generali9ed hives) pruritus or flushing) swollen lips

tongueuvula, AE$ AD <#A'D ;E# ; D# ;<<;GIE4

a. =espiratory co3pro3ise &eg) dyspnea) whee9ebronchospas3)stridor) reduce 5#) hypoxe3ia

b. =educed 5 or associated sy3pto3s of endorgan dysfunction&eg) hypotonia Hcollapse) syncope) incontinence,

am+(on ', et al. JACI 2006;11=:>91-2






ul?lledul?lled 22

. Dwo or 3ore of the following that occur rapidly afterexposure to a likely allergen for that patient &3inutes toseveral hours,:

a. Involve3ent of the s2in3ucosal tissue &eg) generali9ed hives)

itcflush) swollen lipstongueuvula,

b. =espiratory co3pro3ise &eg) dyspnea) whee9ebronchospas3)stridor) reduced 5#) hypoxe3ia

c. =educed 5 or associated sy3pto3s of endorgan dysfunction

&eg) hypotonia Hcollapse) syncope) incontinence,d. 5ersistent gastrointestinal sy3pto3s &eg) cra3py abdo3inal

pain) vo3iting,

A h l # # h# hl l#k l hA h l # # h# hl l#k l h





ul?lledul?lled >>

!. =educed 5 after exposure to known allergen for that patient &3inutes several hours,

a. Infants and children: lowsystolic 5 &age specific, or greater

than !"6 decrease in systolic 5>b. Adults: systolic 5 of less than *" 33 g or greater than !"6

decrease fro3 that personJs baseline

?/, ea! e+iato) *lo"; B, 7loo& +e((ue

< o" ()(tolic 7loo& +e((ue *o c%il&en i( &e*ine& a( le(( t%an =0 mm 'g *om 1 mont% to 1 )ea, le((

t%an =0 mm '@ 2 age3 *om 1 to 10 )ea(, an& le(( t%an 90 mm 'g *om 11 to 1= )ea(.



DIFF%!%&'IA+ DIA5&(SIS (FDIFF%!%&'IA+ DIA5&(SIS (F

A&A)H*+A,ISA&A)H*+A,IS 5asoagal reactions

+lushing

6astocytosis

3arcinoid syndro'e

*yperentilation syndro'e

Glo1us hystericus

*ereditary angioede'a

7ther types of shoc8, eg. cardiogenic, septic )co'1roid poisoning



TREATMENTTREATMENT

E ( E$e*%e/y $&&%e$e( o



E$e*%e/y $&&%e$e( oE$e*%e/y $&&%e$e( o

&&"hyl&'#s&&"hyl&'#s

1. to+ a&mini(tation o* +eci+itant, a((e(( eaction (eeit) an& teatacco&ingl):

Call for assistance

Adrenaline I.3 &lateral thigh, "."1 3g2g up to ".- 3g

i.v access<ie flatelevate legs if tolerated

igh flow oxygen) airwayventilation support if needed

I K5;D#E'IL# A<';:Additional wide bore I.v access &I.e 104 or 1+4 in adults, for nor3al

saline infusion

i.v nor3al saline bolus " 3<2g over 1 3in under pressure

Bo"n, @A. ?meg De& Au(tala(ia. 2006;1E:155-16=

E ( h l #E ( h l #



. If there is inadeuate response) an i33ediate life threat) or deterioration:

And consider also:• ypotension

o =epeat nor3al saline boluses 10-20 mF!g a( nee&e&, u+ to 50mF!g total oe t%e *i(t

>0 mino i.v atropine 0.02 mgF!g i* (eee 7a&)ca&ia minimum &o(e 0.1 mg3

o i. vasopressors to oecome a(o&ilation a(o+e((in 10-40 unit( in a&ult(, ometaaminol 2-10 mg in a&ult(3<. or anaphylactic cardiac arrest, a+i& e(calation to

high dose adrenaline >-53 mg ee) 2-> min3 mig%t 7e e**ectieo I. glucagonphosphodiesterase inhibitorsballon pu3p i* β-7loc!e& o %eat *ailue:

@lucagon &o(e in a&ult(: loa& "it% 1-5 mg oe 5 min, *ollo"e& 7) 5-15 µgFmin<• ronchospas3

o Continuou( salbuta3ol ne7uliGe( o continuou( actuation( o* metee& &o(e in%ale intoentilation cicuit i* intu7ate&3

o i.v. hydrocortisone 5 mgF!g 6 %oul) *ollo"e& 7) oal prednisone 1 mgF!g ma. 50 mg3

*o 4 &a)(• Upper airway obstruction

o e7uliGe& a&enaline 5 mg in H m, I.e. 5 m o* 1:1000 ma) +oi&e (ome elie*o e+ae *o (ugical

tat an I. adrenalin infusion a( +e %o(+ital gui&eline(F+otocolR

Re+eat i.m a&enalin ee) >-5 min a( nee&e&

E$e*%e/y $&&%e$e( o &&"hyl&'#sE$e*%e/y $&&%e$e( o &&"hyl&'#s

Bo"n, @A. ?meg De& Au(tala(ia. 2006;1E:155-16=




> (1serve for an adeuate period and arrange appropriate follo2 up;(1serve for an adeuate period and arrange appropriate follo2 up;i0 (1serve for a minimum of 8 h after the resolution of all sy'pto's

and signs

• 9a8e 1lood for seru' 'ast cell tryptase on arrial, $ h after arrialand prior to discharge.• Ad'it longer oernight; those <ith seere reactions, a history of

lifethreatening reactions or poorly controlled• Asth'a, and those <ho present late in the eening

ii0 (utpatient follo2 up 1y a specialist allergist is reco''ended for allthose <ith 'oderateseere reactions, and <ith 'ild reactions tofood if the patient also has asth'a

Prior to discharge allergen avoidance measures including "edicAlert;. =nsure that an alert is placed in hospital >practicerecords>co'puter syste', and ensure that your referralletter>su''ary contains a detailed record of reaction features &ti'ing, possi1le precipitants and ti'es of exposure

iii0 Arrange for an %pi)en- demonstrate correct use 2ith an %pi)en'rainer and provide a <ritten action plan http:>><<<.allergy.org.au;

if there is a significant ris8 of reexposure and outpatient follo< up<ill 1e delayed


http://www.allergy.org.au/

http://www.allergy.org.au/



Ph&*$&/olo%y o e"#e"h*#ePh&*$&/olo%y o e"#e"h*#e

%pinephrine

9.receptor 6.receptor 9.adrenergic

receptor

6.adrenergic

receptor

↑

vasoconstriction

↑

peripheral vascular resistance↓

mucosal edema

↓ insulin release

↓ neropinephrine release

↑ inotropy

↑

chronotropy

↑ 1ronchodilation

↑

vasodilation↑ glycogenolysis

↓ mucosal edema

%stelle F%!0 # Allergy Clin Immunol 6778>99:;<:.88



A1sorption of epinephrine is fasterA1sorption of epinephrine is faster

after intramuscular inJection than afterafter intramuscular inJection than after

su1cutaneous inJectionsu1cutaneous inJection

%stelle F%!0 # Allergy Clin Immunol 6778>99:;<:.88

:8±

98 3?.9674 minutes

p 707?

? 97 9? 67 6? :7 :?

<± 6 minutes

'ime to Cmax after inJection 3minutes4

Intramuscular

epinephrine

3%pipenL4

Su1cutaneous

epinephrine



PREVENTIONPREVENTION



+(&5 '%!"+(&5 '%!"

A s s e s ! i s $

A s s e s

! i s $

! e d u

c e ! i s $

! e d u

c e ! i s $

EducateEducate

R e c o g n i z e

ACUTE

T r e a t

Prevent

FI5 60 'he dual role of the allergy.immunology specialist in anaphylaxisFI5 60 'he dual role of the allergy.immunology specialist in anaphylaxis

Simons F0%0! #ACI 677=>99;:=.:Simons F0%0! #ACI 677=>99;:=.:



Mhy is follo2 up is needed NMhy is follo2 up is needed N

Anaphylaxis can occur repeatedly

'he trigger need to 1e confirmed

+ong.term preventive strategies

need to 1e implemented



Edu/&(#o o &&"hyl&'#sEdu/&(#o o &&"hyl&'#s

Individuals and their fa3ilies

Caregivers

ealth case professional &doctors) nurses,

irst respondent

#3ergency 3edical services

Deachers coaches) child care providers

ood industries) restaurant) law 3a2ers



90 )rior History . Identification90 )rior History . Identification



60 "edical alert 1rachelet60 "edical alert 1rachelet99



"edical alert 1rachelet"edical alert 1rachelet66



)revention)revention99



:0 %mergency Kit:0 %mergency Kit



)revention)revention66

)harmacologic prophylaxis ; !C"

Immunotherapy

Hidden allergens- cross reactivity Maiting :7 minutes after inJections

S l Ch f C dS l Ch f C d



Sample Chef CardSample Chef Card'o the Chef;'o the Chef;

MA!&I&5O I am allergic to peanuts0 In order to avoid a life.threateningreaction- I must avoid the follo2ing ingredients;

Artificial nuts

Peer nuts

Cold pressed- expelled- or extruded peanut oil

5round nuts

"andelonas

"ixed nuts

"on$ey nuts

&ut pieces

)eanut

)eanut 1utter )eanut flour

)lease ensure any utensils B euipment used to prepare my meal- as

2ell as prep surfaces- are thoroughly cleaned prior to use0 'han$s for

your cooperation

"uno/0 Anaphylaxis 67780 Miley- Chichester0 )0 6=?.?

Anafilaksis (PIT 2008)

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